Process for the manufacture of esters of hydroxy carboxylic acids



Patented Aug. 24, 1948 PROCESS FOR THE MANUFACTURE OF ESTERS OF .HYDROXY CARBOXYLIC ACIDS Edward M. Filaehione, Philadelphia, and Charles 11. Fisher, Abington, Pm, minors to United States of America as represented by the Secretary of Agriculture No Drawing. Application December 23, 1945, Serial No. 888,484

3 Claims. (Cl. 260-484) (Granted under the m of March a, 1883, as amended April so, 192s; are 0. o. 157) p This application is made under the act of March 3, 1883, as amended by the act of April 30, 1928, and the invention herein described, if patented, may be manufactured and used by or for the Government of the United States of America. for governmental purposes without the payment to us of any royalty thereon.

This application is a continuation-in-part of our copending application for patent, Serial No. 493,706, filed July 7, 1943, now abandoned.

This invention relates to the preparation of esters of hydroxy carboxylic acids, and more particularly to the preparation of alkyl and alkenyl esters of hydroxy acids such as methyl lactate, ethyl lactate, allyl glycolate, and allyl lactate.

It is known that unusual difficulties are experienced in converting hydroxy carboxylic acids into their esters. Hydroxy acids may be considered as alcohols as well as carboxylic acids because of the presence in the molecule of one or more alcoholic hydroxyl groups. During esterification, the esterifying alcohol is afforded competition by the alcoholic hydroiq'l group of the hydroxy acid. As a consequence, a large excess of the alcohol is usually employed. Also, it is especially difllcult to prepare the methyl ester of hydroxy acids because of the low boiling point of methanol. when the reaction mixture is distilled to separate the products, the unchanged methanol distils first, leaving a mixture containing water and the hydroxy ester, so that hydrolysis of the hydroxy ester occurs as the distillation is continued. This undesirable hydrolysis is particularly evident when the alcohol concerned has a boiling point lower than that of water.

An object of our invention, therefore, is to provide an improved method of manufacturing hydroxy esters, particularly the lower alkyl and alkenyl esters of hydroxy acids.

A further object is to provide a method of manufacturing hydroxy esters which obviates difllculties ordinarily experienced in preparing hydroxy esters.

A further object is to provide a method of manufacturing hydroxy esters under essentially anhydrous conditions, or in an environment containing a minimum quantity of water.

A further object is to provide a method of manufacturing hydroxy esters in such a manner that the products obtained are readily separable by distillation.

A further object is to provide a method of manufacturing hydroxy esters at any desired temperature, regardless of the boiling point of the alcohol.

A further object is to utilize the principle attributed to Le Chatelier by applying pressure and forcing the esteriflcation, or alcoholysis, in the desired direction.

Other objects will appear from the following description of the invention.

Our invention is particularly suited for the preparation of alkyl and alkenyl esters such as methyl lactate, ethyl lactate, allyl glycolate, and allyl lactate. Lactic acid has been converted into methyl and ethyl lactates by several methods, but each of the methods previously used has certain disadvantages. Thus, in most cases, the yields of methyl and ethyl lactate actually obtained are low. Also, when alkyl lactates are prepared from metal lactates, a troublesome filtration is required, and care must be taken to remove the water of crystallization prior to esterification if the presence of considerable water in the esteriflcation mixture is to be avoided.

Again, a satisfactory method for removing water of reaction is not provided in most methods previously employed to prepare methyl and ethyl lactates. This is especially important because, as previously mentioned, the water of reaction, if present during distillation, causes hydrolysis and loss of lactic ester, particularly if the ester is methyl lactate. Moreover, water is objectionable in the esterification mixture because equilibrium is established in the presence of water, and high yields of ester are not obtainable under these conditions. A further obj'ection to some methods of preparing lactic esters is that a large excess of alcohol is required. An objection to most methods for making the lower lactic esters is that, owing to the low boiling points of the lower alcohols, the refluxing temperature is low, and relatively long periods of refluxing are required for the esteriflcation.

We have found that condensation polymers of hydroxy acids, such as glycolic acid and lactic acid, of high molecular weight, react readily with lower alcohols having not more than six carbons and which may be saturated or unsaturated, such as methyl alcohol, ethyl alcohol, crotyi alcohol, lnethaliyl alcohol, chloroallyl alcohol and allyl alcohol, particularly if the reaction is carried out in a closed Vessel at temperatures above the boiling point of the alcohol at atmospheric pressure, this temperature generally ranging about from 100 to 150 C. These condensation polymers include the dimers, trimers, and so forth, of the hydroxy acids which are produced by the seif-esterification of the acid, and which will be hereinafter designated by the prefix poly-, like polyglycolic acid, polyiactic acid, and so forth. The condensation polymers include also the condensation products obtained by the reaction of condensation of mixtures of different hydroxy polymerization reaction, may be added to the lactic acid prior to removal of water, and the resulting polymers may be esterifled as described herein.

Our invention is illustrated by the examples set forth in the following table. The reactions were carried out by placing the reactants in a pressure vessel and heating at the temperatures indicated. Glass (Magnesia") bottles were used for the experiments carried out at 100 C., and an autoclave was employed for the reactions conducted at higher temperatures. As indicated in the table, acid catalysts were used. At the end of the reaction, the catalyst was neutralized with sodium acetate, or some suitable base, and distilled.

CONVERSION OF LACTIC ACID POLYMERS INTO METHYL LACTATE Polymerized M e thanol Acid catalyst lactic acid T T lgtznverililoli Exam is No. gimp me, me y p Equiv- Dehydm Amount, 0' hrs a ift' per slants tiool,n per Moles Ratio Acid cm 0; 5 94 l. 2. 5 0. 25 150 4 75 0. 5 70 0. 5 1.0 0. 5 150 4 33 0. 5 70 1. 25 2. 5 0. 5 1.50 4 70 0. 2. 27 5.0 0. 45 150 4 80 0. 5 70 l. 25 2. 5 0. 5 150 2 73 0. 5 70 1.25 2. 5 0. 5 150 l 76 0. 5 70 0. 5 1.0 0. 5 100 4 5i 0. 5 70 2. 5 2. 5 0. 5 100 4 76 0. 5 70 2. 5 5. 0 0. 5 100 4 0. 5 70 5. 0 l0. 0 0. 5 100 4 78 0. 5 70 2. 5 5. 0 0. 5 100 2 78 0. 5 70 2. 5 5.0 0. 5 100 l 84 0. 5 70 2. 5 5.0 1.4 g. 100 2 74 1. 0 70 2. 5 2. 5 1.0 100 4 76 1.0 70 2. 5 2. 5 0. 5 100 4 70 1. 0 70 2. 5 2. 5 0. 25 100 4 80 0. 5 8i 2. 5 5. 0 0. 5 100 4 -88 0. 5 83 2. 5 5.0 0. 5 100 4 84 0. 5 2. 5 5.0 p-tolliiene sul- 0.5 g. 4 81 on c.

acids and of mixtures of a hydroxy acid and an aliphatic, polyhydric alcohol containing not more than three hydroxyl groups, such as a mixture of lactic acid and glycolic acid, a mixture of lactic acid, glycolic acid, and glycerol, 9. mixture of lactic acid and various glycois, and other mixtures. We prefer to use these latter polymers, which are hereinafter designated as condensation products and which are prepared by removing almost one mole of water from each mole of the hydroxy acid, rather than using the dimers or trimers of the hydroxy acids, which, however, are also applicable to the invention.

Thus, we have found, for examp1e,-that lactic acid condensation polymers prepared by removing 60 percent or more of the theoretical amount of water, are especially suitable for conversion into esters. We have found also that these lactic acid condensation polymers react with the lower alcohols to give high yields of the corresponding ester, even when only a small excess of the alcohol is used, and that a relatively short reaction time is required. By using a lactic acid condensation polymer of relatively high molecular weight, a product is obtained which contains little water and which is easily separated from the other products present in the reaction mixture. The lactic acid polymer can be made by removing the required amount of water from lactic acid in a vacuum, or at atmospheric pressure at elevated temperatures. An entraining agent such as benzene, toluene, ethylene chloride, and ligroin may be added to facilitate removal of the water. Other materials such as alcohols, glycols, hydroxy acids, or amino alcohols which will enter the The conversion into methyl lactate, as indicated in the last column of the table, does not take into account the distillation residues which can be further utilized for the production of lactic acid or methyl lactate.

In addition to the foregoing examples, shown in the above table, allyl glycolate was prepared from polyglycolic acid, and allyl lactate was obtained from the condensation product of lactic acid and glycerol. The preparation of these compounds, in addition to a further example of the preparation of methyl lactate from the condensation product of lactic acid and glycerol, is illustrated in greater detail in the following additional examples.

Exmn: 20

Preparation of allyl glycolate Glycolic acid, containing approximately 70 percent hydroxyacetic acid and 30 percent water, was treated with a small quantity of concentrated sulfuric acid, and the resulting mixture was heated under reduced pressure. Water distilled, yielding polymeric or dehydration products of glycolic acid, hereinafter referred to as polyglycolic acid.

Thirty-one grams of polyglycolic acid, 0.13 ml. of sulfuric acid, and 146 g. of allyl alcohol were heated in a bomb at about from to 139 C. for about 6 hours. The resulting mixture was then treated with 0.6 g. sodium acetate and distilled under reduced pressure.

Allyl glycolate was obtained as the fraction distilling at about from 60 to 72 C. under 8 mm,

mercury pressure and was found to have the following physical constants:

n 1.4418; and di= 1.090

mun-1.: 21

Preparation of allul lactate from glycerol-lactic acid condensation product A glycerol-lactic acid condensation product was prepared as described below:

A mixture of 330 g. of 81.7 percent lactic acid (containing 3 equivalents of lactic acid), 92 g. (1 mole) of glycerol, and 0.75 ml. of concentrated sulfuric acid was heated in vacuum (40 mm. of mercury pressure) using a water bath as the source of heat. After about 3 hours, during which time the bath temperature was raised to about 100 0., there was collected 116 g. of distillate, which was essentially water. The condensation products, 307 g., which remained in the still pot was a pale yellow viscous liquid.

A mixture of 50.5 g. of the glycerol-lactic acid condensation product, 0.25 ml. 'of concentrated sulfuric acid, and 2.5 moles of allyl alcohol was heated in a bomb having a glass liner for about 2 hours at about from 120 to 130 (3., the 50.5 g. of condensation product being equivalent to 0.5 mole of lactic acid. The reaction mixture was removed from the bomb, treated with 0.5 g. sodium acetate, and distilled under reduced pressure. A 73 percent yield of allyl lactate was obtained and the glycerol, being recovered by vacuum distillation, contained approximately percent lactide.

Exmu 22 Preparation of methyl lactate from glycerol-lactic acid condensation product A mixture of 50.7 g. of the condensation prodnot, 80 g. of methanol, and 0.13 ml. of concentrated sulfuric acid was then heated in a closed' glass vessel at about 100 C. for about 3.5 hours, forming methyl lactate. The methyl lactate was isolated from the reaction mixture by adding 1 g. of sodium acetate thereto, distilling themethanol at atmospheric pressure, and then distilling the methyl lactate under 23 mm. of mercury pressure. The yield of methyl lactate was found to be 86 percent. The glycerol was recovered from the reaction mixture by vacuum distillation.

The esteriflcation reactions can also be carried out by refluxing at atmospheric pressure, but the reaction rate is lower and the reaction temperature is limited by the boiling point of the alcohol. Thus, by refluxing polylactic acid (one equivalent) with methanol in the presence of p-toluenesulfonic acid (0.5 to 1.0 g.) for about from 7 to 10 hours, .a 50 to 68 percent conversion to methyl lactate was obtained.

The reaction is applicable also to the formation of other lactates. For example, a 5'1 P rcent yield of ethyl lactate was obtained when polylactic acid (one equivalent and ethanol (2.5 moles) containing 1.0 cc. of concentrated sulfuric acid was heated for 4 hours at 100 C.

Although our invention is specifically illustrated by the examples given above, it is not limited to the particular materials or procedures disclosed. It will be apparent to those skilled in the art that various modifications of procedure may be employed. For. example, a third material may be included with the reagents to facilitate separation of the products by formation of constant boiling mixtures. Materials such as ethylene oxide, alkyl sulfates, alkyl phosphates, or alkyl borates, may be used in the esteriflcation reaction to remove small amounts of water that might be present. The reaction may be carried out under high pressures of nitrogen, carbon dioxide, or other gases. The distillation residue of one run may be added to the reactants of a later preparation.

Continuous operation of our process is also practicable. For example, a condensation polymer of lactic acid may be dissolved in about from 3 to 6 parts, by weight, of alcohol. If sludge, or other solids are present, the solution may be illtered. A small quantity of a mineral acid is then added, and the solution is pumped by means of any suitable pump, such as the Milton Roy pump, into and through a stainless steel chamber maintained at about from to C. The rate of pumping and the size of the chamber should be selected so that the solution is in the heated chamber about from one-half to one hour, although a longer or a shorter residence time may be used. Various modifications can be used in one of which, for example, the alcohol and condensation polymer could be pumped separately into the heated chamber. After the reaction is complete, the mixture is withdrawn from the chamber through a suitable valve located below the liquid level, and the material thus withdrawn contains the hydroxy ester and some unconverted condensation polymers of lactic acid. This material may be condensed, neutralized, and distilled, continuously or in batches, to recover the pure hydroxy ester, and the residue may then be recycled. Also, the material in its withdrawn form may be used as such for other purposes, including acylation prior to pyrogenic conversion into acrylic esters.

Having thus described our invention, we claim:

1. A process of manufacturing an ester of a hydroxy carboxylic acid comprising heating a mixture containing a hydroxy carboxylic acid selected from the group consisting of glycolic acid and lactic acid and an aliphatic, polyhydric alcohol containing not more than three hydroxyl groups, in the presence of an acid catalyst, removing the water formed during the reaction from the condensation product thus produced, and reacting, in the liquid phase, the said condensation product with an alkenol having not more than 6 carbon atoms in the presence of an acid catalyst at a temperature of about from 100 C. to 150 C.

2. The process of claim 1 wherein the alkenol is allyl alcohol.

3. A process of manufacturing allyl lactate comprising heating a mixture containing glycerol and lactic acid in the presence of an acid catalyst, removing the ater formed during the reaction Jm the glycerol-lactic acid condensation product thus produced, and reacting, in the liquid phase, the said condensation product with allyl alcohol in the presence of a catalytic amount of sulfuric acid at a temperature of about from 100 C. to 150 C.

EDWARD M. FILACHIONE. CHARLES H. FISHER.

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